Federal Register, Volume 76 Issue 105 (Wednesday, June 1, 2011)

[Federal Register Volume 76, Number 105 (Wednesday, June 1, 2011)]
[Rules and Regulations]
[Pages 31471-31479]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2011-13577]

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ENVIRONMENTAL PROTECTION AGENCY

40 CFR Part 180

[EPA-HQ-OPP-2011-0361; FRL-8870-7]

Ethylene Glycol; Exemption From the Requirement of a Tolerance

AGENCY: Environmental Protection Agency (EPA).

ACTION: Final rule.

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SUMMARY: This regulation establishes an exemption from the requirement
of a tolerance for residues of ethylene glycol (CAS Reg. No. 107-21-1)
when used as a pesticide inert ingredient as a solvent, stabilizer and/
or antifreeze within pesticide formulations/products without
limitation. Huntsman, et. al, submitted a petition to EPA under the
Federal Food, Drug, and Cosmetic Act (FFDCA), requesting an
establishment of an exemption from the requirement of a tolerance. This
regulation eliminates the need to establish a maximum permissible level
for residues of ethylene glycol. Also, this regulation establishes an
exemption from the requirement of a tolerance for residues of ethylene
glycol (CAS Reg. No. 107-21-1) when used as an inert ingredient as an
encapsulating agent for pesticides being applied post-harvest as
residual, and crack and crevice sprays in and around food and nonfood
areas of residential and nonresidential structures, including food
handling establishments, with no limit. The Sumitomo Chemical Company
submitted a petition to EPA under FFDCA, requesting an establishment of
an exemption from the requirement of a tolerance. This regulation
eliminates the need to establish a maximum permissible level for
residues of ethylene glycol.

[[Page 31472]]

DATES: This regulation is effective June 1, 2011. Objections and
requests for hearings must be received on or before August 1, 2011, and
must be filed in accordance with the instructions provided in 40 CFR
part 178 (see also Unit I.C. of the SUPPLEMENTARY INFORMATION).

ADDRESSES: EPA has established a docket for these actions under docket
identification (ID) number EPA-HQ-OPP-2011-0361. All documents in the
docket are listed in the docket index available at http://www.regulations.gov. Although listed in the index, some information is
not publicly available, e.g., Confidential Business Information (CBI)
or other information whose disclosure is restricted by statute. Certain
other material, such as copyrighted material, is not placed on the
Internet and will be publicly available only in hard copy form.
Publicly available docket materials are available in the electronic
docket at http://www.regulations.gov, or, if only available in hard
copy, at the OPP Regulatory Public Docket in Rm. S-4400, One Potomac
Yard (South Bldg.), 2777 S. Crystal Dr., Arlington, VA. The Docket
Facility is open from 8:30 a.m. to 4 p.m., Monday through Friday,
excluding legal holidays. The Docket Facility telephone number is (703)
305-5805.

FOR FURTHER INFORMATION CONTACT: Lisa Austin, Registration Division
(7505P), Office of Pesticide Programs, Environmental Protection Agency,
1200 Pennsylvania Ave., NW., Washington, DC 20460-0001; telephone
number: (703) 305-7894; e-mail address: austin.lisa@epa.gov.

SUPPLEMENTARY INFORMATION:

I. General Information

A. Does this action apply to me?

You may be potentially affected by this action if you are an
agricultural producer, food manufacturer, or pesticide manufacturer.
Potentially affected entities may include, but are not limited to:
Crop production (NAICS code 111).
Animal production (NAICS code 112).
Food manufacturing (NAICS code 311).
Pesticide manufacturing (NAICS code 32532).
This listing is not intended to be exhaustive, but rather provides
a guide for readers regarding entities likely to be affected by this
action. Other types of entities not listed in this unit could also be
affected. The North American Industrial Classification System (NAICS)
codes have been provided to assist you and others in determining
whether this action might apply to certain entities. If you have any
questions regarding the applicability of this action to a particular
entity, consult the person listed under FOR FURTHER INFORMATION
CONTACT.

B. How can I get electronic access to other related information?

You may access a frequently updated electronic version of 40 CFR
part 180 through the Government Printing Office's e-CFR site at http://www.gpoaccess.gov/ecfr.

C. How can I file an objection or hearing request?

Under FFDCA section 408(g), 21 U.S.C. 346a, any person may file an
objection to any aspect of this regulation and may also request a
hearing on those objections. You must file your objection or request a
hearing on this regulation in accordance with the instructions provided
in 40 CFR part 178. To ensure proper receipt by EPA, you must identify
docket ID number EPA-HQ-OPP-2011-0361 in the subject line on the first
page of your submission. All objections and requests for a hearing must
be in writing, and must be received by the Hearing Clerk on or before
August 1, 2011. Addresses for mail and hand delivery of objections and
hearing requests are provided in 40 CFR 178.25(b).
In addition to filing an objection or hearing request with the
Hearing Clerk as described in 40 CFR part 178, please submit a copy of
the filing that does not contain any CBI for inclusion in the public
docket. Information not marked confidential pursuant to 40 CFR part 2
may be disclosed publicly by EPA without prior notice. Submit a copy of
your non-CBI objection or hearing request, identified by docket ID
number EPA-HQ-OPP-2011-0361, by one of the following methods:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the on-line instructions for submitting comments.
Mail: Office of Pesticide Programs (OPP) Regulatory Public
Docket (7502P), Environmental Protection Agency, 1200 Pennsylvania
Ave., NW. Washington, DC 20460-0001.
Delivery: OPP Regulatory Public Docket (7502P),
Environmental Protection Agency, Rm. S-4400, One Potomac Yard (South
Bldg.), 2777 S. Crystal Dr., Arlington, VA. Deliveries are only
accepted during the Docket Facility's normal hours of operation (8:30
a.m. to 4 p.m., Monday through Friday, excluding legal holidays).
Special arrangements should be made for deliveries of boxed
information. The Docket Facility telephone number is (703) 305-5805.

II. Petition for Exemption

EPA received two petitions requesting that 40 CFR 180.910 and 40
CFR 180.920 be amended by establishing an exemption from the
requirement of a tolerance for residues of ethylene glycol.
In the Federal Register of July 9, 2008 (73 FR 39291) (FRL-8371-2),
EPA issued a notice pursuant to section 408 of FFDCA, 21 U.S.C. 346a,
announcing the filing of a pesticide petition (PP 8E7355) by Huntsman,
10003 Woodloch Forest Drive, The Woodlands, TX 77380; Dow AgroSciences
L.L.C., 9330 Zionsville Road, Indianapolis, Indiana 46268; Nufarm
Americas Inc., 150 Harvester Drive Suite 220, Burr Ridge, Illinois
60527; BASF, 26 Davis Drive, Research Triangle Park, NC 27709; Stepan
Company, 22 W. Frontage Road, Northfield, IL 60093; Loveland Products
Inc., PO Box 1286, Greeley, CO 80632; and Rhodia Inc., CN 1500,
Cranbury, New Jersey 08512. The petition requested that 40 CFR 180.920
be amended by establishing an exemption from the requirement of a
tolerance for residues of ethylene glycol (CAS Reg. No. 107-21-1) when
used as an inert ingredient solvent, stabilizer and/or antifreeze
without limitation in pesticide formulations applied to pre-harvest
crops. That notice referenced a summary of the petition prepared by
Huntsman, Dow AgroSciences L.L.C., Nufarm Americas Inc., BASF, Stepan
Company, Loveland Products Inc., and Rhodia Inc., which is available in
the docket, http://www.regulations.gov. The Agency received one comment
in response to the notice of filing.
Also, in the Federal Register of August 4, 2004 (69 FR 47149) (FRL-
7367-7), EPA issued a notice pursuant to section 408 of FFDCA, 21
U.S.C. 346a, announcing the filing of a pesticide petition (PP 4E6828)
by the Sumitomo Chemical Company, Ltd., 5-33 Kitahama, 4-chrome, chuo-
ku, Osaka 541-8550 Japan. The petition requested that 40 CFR 180.910 be
amended by establishing an exemption from the requirement of a
tolerance for residues of ethylene glycol (CAS Reg. No. 107-21-1) when
used as an inert ingredient in encapsulating agents for pesticides
being applied post-harvest as residual, and crack and crevice sprays in
and around food and nonfood areas of residential and nonresidential
structures, including food handling establishments, with no limit. That
notice referenced a summary of the petition prepared by the Sumitomo
Chemical Company, which is available

[[Page 31473]]

in the docket, http://www.regulations.gov. The Agency received one
comment in response to the notice of filing.

III. Inert Ingredient Definition

Inert ingredients are all ingredients that are not active
ingredients as defined in 40 CFR 153.125 and include, but are not
limited to, the following types of ingredients (except when they have a
pesticidal efficacy of their own): Solvents such as alcohols and
hydrocarbons; surfactants such as polyoxyethylene polymers and fatty
acids; carriers such as clay and diatomaceous earth; thickeners such as
carrageenan and modified cellulose; wetting, spreading, and dispersing
agents; propellants in aerosol dispensers; microencapsulating agents;
and emulsifiers. The term ``inert'' is not intended to imply
nontoxicity; the ingredient may or may not be chemically active.
Generally, EPA has exempted inert ingredients from the requirement of a
tolerance based on the low toxicity of the individual inert
ingredients.

IV. Aggregate Risk Assessment and Determination of Safety

Section 408(c)(2)(A)(i) of FFDCA allows EPA to establish an
exemption from the requirement for a tolerance (the legal limit for a
pesticide chemical residue in or on a food) only if EPA determines that
the tolerance is ``safe.'' Section 408(b)(2)(A)(ii) of FFDCA defines
``safe'' to mean that ``there is a reasonable certainty that no harm
will result from aggregate exposure to the pesticide chemical residue,
including all anticipated dietary exposures and all other exposures for
which there is reliable information.'' This includes exposure through
drinking water and in residential settings, but does not include
occupational exposure. Section 408(b)(2)(C) of FFDCA requires EPA to
give special consideration to exposure of infants and children to the
pesticide chemical residue in establishing a tolerance and to ``ensure
that there is a reasonable certainty that no harm will result to
infants and children from aggregate exposure to the pesticide chemical
residue * * *.''
EPA establishes exemptions from the requirement of a tolerance only
in those cases where it can be clearly demonstrated that the risks from
aggregate exposure to pesticide chemical residues under reasonably
foreseeable circumstances will pose no appreciable risks to human
health. In order to determine the risks from aggregate exposure to
pesticide inert ingredients, the Agency considers the toxicity of the
inert in conjunction with possible exposure to residues of the inert
ingredient through food, drinking water, and through other exposures
that occur as a result of pesticide use in residential settings. If EPA
is able to determine that a finite tolerance is not necessary to ensure
that there is a reasonable certainty that no harm will result from
aggregate exposure to the inert ingredient, an exemption from the
requirement of a tolerance may be established.
Consistent with section 408(c)(2)(A) of FFDCA, and the factors
specified in FFDCA section 408(c)(2)(B), EPA has reviewed the available
scientific data and other relevant information in support of this
action. EPA has sufficient data to assess the hazards of and to make a
determination on aggregate exposure for ethylene glycol including
exposure resulting from the exemption established by this action. EPA's
assessment of exposures and risks associated with ethylene glycol
follows.

A. Toxicological Profile

EPA has evaluated the available toxicity data and considered their
validity, completeness, and reliability as well as the relationship of
the results of the studies to human risk. EPA has also considered
available information concerning the variability of the sensitivities
of major identifiable subgroups of consumers, including infants and
children. Specific information on the studies received and the nature
of the adverse effects caused by ethylene glycol as well as the no-
observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-
effect-level (LOAEL) from the toxicity studies are discussed in this
unit.
Acute oral toxicity in rodents, as expressed as a lethal dose
(LD)50, ranges from 1,500 milligram/kilogram (mg/kg) to
8,800 mg/kg. In the guinea pig, the acute oral toxicity is about 6,600
mg/kg and in the rabbit, 5,000 mg/kg. In the dog, the acute oral
LD50 is greater than 8,000 mg/kg. It is minimally irritating
to the eyes and skin of rabbits. Acute inhalation and dermal toxicity
data were not identified. However, given the vapor pressure of
undiluted ethylene glycol (0.092 millimeter (mm) mercury (Hg) @ 25
[deg]C) acute inhalation concerns are not expected. According to the
National Institute of Occupational Safety and Health (NIOSH) (1999), a
``harmful contamination of the air will be reached rather slowly on
evaporation of this substance at 20 [deg]C.''
In subchronic and chronic testing, rats were more sensitive to the
effects of ethylene glycol treatment than mice at comparable dose
levels. Among rats, males appeared to be more sensitive than females.
In subchronic toxicity testing in rats and mice, the kidney was
adversely affected in all studies considered. Effects common to all
studies include increased kidney weights, formation of lesions, and
formation of oxalate crystals. In the rat, NOAELs range from 71 to
4,000 mg/kg/day and in the mouse the NOAELs range from 1,000 to 3,230
mg/kg/day. In chronic testing in rats, kidney effects similar to those
seen in subchronic testing were observed. In addition, effects to the
liver were seen (i.e., decreased liver weight; fatty changes). The
lowest NOAEL (71 mg/kg/day) in the toxicity database occurred in a
subchronic toxicity study in rats. The LOAEL in this study was 180 mg/
kg/day based on kidney effects. In chronic studies, the lowest NOAEL of
150 mg/kg/day was observed in rats, the most sensitive species.
Developmental toxicity testing was conducted in rats, mice, and
rabbits. Overall, fetal toxicity was exhibited as increased fetal
deaths, skeletal and external malformations, and reduced body weight.
Maternal toxicity was manifested as decreased body weight gain, kidney
effects (lesions, increased organ weight), and liver effects (decreased
organ weight). The relative sensitivities of these species in terms of
developmental toxicity during organogenesis are: Mice are the most
sensitive and rabbits are the least sensitive. For maternal toxicity
per se the sensitivity is: Rats are the most sensitive and rabbits are
the least sensitive.
In rabbits, statistically-significant fetal developmental toxicity
was not observed; however, maternal toxicity was seen at 2,000 mg/kg/
day; it was manifested as renal toxicity (lesions, oxalate formation).
In rats, fetal toxicity was seen at doses ranging from 1,000 mg/kg/day
to 2,500 mg/kg/day. It manifested as decreased viability (2,250 mg/kg/
day); decreased body weight gain and decreased pup weight (1,000 to
2,500 mg/kg/day); and skeletal effects and malformations (1,000 to
2,500 mg/kg/day). The skeletal effects and malformations included:
Poorly ossified and unossified vertebral centra; decrease in total
ossification; hydrocephaly; and pup malformation. Maternal toxicity in
rats was manifested as: Decreased body weight gain (1,250 to 2,500 mg/
kg/day); decreased liver weight (5,000 mg/kg/day); and kidney effects
such as lesions and increased weight (1,250 to 2,500 mg/kg/day). In
mice, fetal toxicity was seen at doses ranging from 500 to 1,500 mg/kg/
day. As with rats it manifested as decreased

[[Page 31474]]

fetal body weight and/or weight gain (750 to 1,500 mg/kg/day) and
skeletal effects (500 to 1,500 mg/kg/day) which included: Pup
malformations, fused ribs and arches, poor ossification in thoracic and
lumbar centra, and increased occurrence of an extra 14th rib. The
lowest developmental NOAEL in mice was 150 mg/kg/day. Maternal toxicity
was demonstrated as decreased weight gain (1,500 mg/kg/day) and
decreased liver weight (1,500 mg/kg/day).
The reproductive toxicity of ethylene glycol was studied in rats
and mice. In rats, no reproductive toxicity was noted. In mice,
reproductive toxicity was seen at doses ranging from 897 to 2,826 mg/
kg/day. It manifested as: Decreased numbers of live implants and
increased number of dead implants; sperm effects (abnormal sperm,
decreased motility, decreased sperm count); testicular lesions; and
decreased testes weight.
Ethylene glycol is not known to be mutagenic. In a standard battery
of in vitro genotoxicity assays conducted by the National Toxicology
Program; Health and Human Services (NTP; HHS 1993), all results were
negative. Ethylene glycol is not considered to be carcinogenic. In
carcinogenicity testing conducted by the NTP in rats and mice, no
evidence of carcinogenic potential was noted. Therefore, based on the
lack of mutagenicity and lack of carcinogenicity in rodents, ethylene
glycol is not expected to pose a carcinogenic risk in humans.
Metabolism studies demonstrated that ethylene glycol was rapidly
absorbed, metabolized and excreted. It is primarily metabolized via the
liver and kidneys. Ethylene glycol and metabolites (glycolic acid and
oxalic acid) are primarily excreted in the urine within 12-18 hours
after administration.
Specific information on the studies received and the nature of the
adverse effects caused by the ethylene glycol, as well as, the NOAEL
and the LOAEL from the toxicity studies can be found at http://www.regulations.gov in the document ``800009, Ethylene Glycol; Human
Health Risk Assessment and Ecological Effects Assessment to Support
Proposed Exemption from the Requirement of a Tolerance When Used as
Inert Ingredients in Pesticide Formulations,'' pp. 7-24 in EPA-HQ-OPP-
2008-0474 and EPA-HQ-OPP-2004-0207.

B. Toxicological Points of Departure/Levels of Concern

Once a pesticide's toxicological profile is determined, EPA
identifies toxicological points of departure (POD) and levels of
concern (LOC) to use in evaluating the risk posed by human exposure to
the pesticide. For hazards that have a threshold below which there is
no appreciable risk, the toxicological POD is used as the basis for
derivation of reference values for risk assessment. PODs are developed
based on a careful analysis of the doses in each toxicological study to
determine the dose at which the NOAEL and the LOAEL are identified.
Uncertainty/safety factors are used in conjunction with the POD to
calculate a safe exposure level--generally referred to as a population-
adjusted dose (PAD)(acute = a and chronic = c) or a reference dose
(RfD)--and a safe margin of exposure (MOE). For non-threshold risks,
the Agency assumes that any amount of exposure will lead to some degree
of risk. Thus, the Agency estimates risk in terms of the probability of
an occurrence of the adverse effect expected in a lifetime. For more
information on the general principles EPA uses in risk characterization
and a complete description of the risk assessment process, see http://www.epa.gov/pesticides/factsheets/riskassess.htm.
A summary of the toxicological endpoints for ethylene glycol used
for human risk assessment is shown in the Table of this unit.
No acute endpoint of concern for general population was identified
in the available data base. However, the endpoint of concern for
females 13 plus age was identified in a developmental toxicity study in
mice with a NOAEL of 150 mg/kg/day and LOAEL of 500 mg/kg/day based on
an increased incidence of total malformations and bilateral extra
rib14.
The endpoint selected for the cRfD was based on a chronic toxicity
study in rats. The NOAEL in this study was 150 mg/kg/day based on
kidney lesions and mortality observed at 300 mg/kg/day. Although 71 mg/
kg/day is the lowest NOAEL in the database identified in a subchronic
study in rats, the confidence in this subchronic study is low because
subchronic and chronic studies support the NOAEL of 150 mg/kg/day and
above. The NOAEL 150 mg/kg/day selected for the cRfD is protective of
any developmental effects. Therefore, the Agency selected the point of
departure of 150 mg/kg/day to establish the cRfD.
The EPA Integrated Risk Information System (IRIS) established a
oral cRfD based on the NOAEL of 200 mg/kg/day and uncertainty factor
100. The currently chosen endpoint and the dose used for this risk
assessment provide the most conservative assessment.

Table--Summary of Toxicological Doses and Endpoints for Ethylene Glycol for Use in Human Risk Assessment
----------------------------------------------------------------------------------------------------------------
Point of departure and
Exposure/scenario uncertainty/safety RfD, PAD, LOC for risk Study and toxicological effects
factors assessment
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Acute dietary (Females 13-50 NOAEL = 150 mg/kg/day. Acute RfD = 1.5 mg/kg/ Developmental toxicity study--
years of age). UFA = 10x............. day. mice.
UFH = 10x............. aPAD = 1.5 mg/kg/day.. LOAEL = 500 mg/kg bw/day, based
FQPA SF = 1x.......... on increased incidence of total
malformations and bilateral
extra rib 14.
Chronic dietary (All NOAEL = 150 mg/kg/day. Chronic RfD = 1.5 mg/ Chronic toxicity study.
populations). UFA = 10x............. kg/day. LOAEL = 300 mg/kg/day based on
UFH = 10x............. cPAD = 1.5 mg/kg/day.. kidney lesions and death in
FQPA SF = 1x.......... males.
Incidental oral short-term (1 NOAEL = 150 mg/kg/day. LOC for MOE = 100..... Chronic toxicity study.
to 30 days). UFA = 10x............. LOAEL = 300 mg/kg/day based on
UFH = 10x............. kidney lesions and death in
FQPA SF = 1x.......... males.
Incidental oral intermediate- NOAEL = 150 mg/kg/day. LOC for MOE = 100..... Chronic toxicity study.
term (1 to 6 months). UFA = 10x............. LOAEL = 300 mg/kg/day based on
UFH = 10x............. kidney lesions and death in
FQPA SF = 1x.......... males.

[[Page 31475]]

Dermal short-term (1 to 30 NOAEL = 150 mg/kg/day LOC for MOE = 100..... Chronic toxicity study.
days). (dermal absorption LOAEL = 300 mg/kg/day based on
rate = 25%. kidney lesions and death in
UFA = 10x............. males.
UFH = 10x.............
FQPA SF = 1x..........
Dermal intermediate-term (1 to NOAEL = 150 mg/kg/day LOC for MOE = 100..... Chronic toxicity study.
6 months). (dermal absorption LOAEL = 300 mg/kg/day based on
rate = 25% when kidney lesions and death in
appropriate). males.
UFA = 10x.............
UFH = 10x.............
FQPA SF = 1x..........
Inhalation short-term (1 to 30 NOAEL = 150 mg/kg/day LOC for MOE = 100..... Chronic toxicity study.
days). (inhalation LOAEL = 300 mg/kg/day based on
absorption rate = kidney lesions and death in
100%). males.
UFA = 10x.............
UFH = 10x.............
FQPA SF = 1x..........
Inhalation (1 to 6 months).... NOAEL = 150 mg/kg/day LOC for MOE = 100..... Chronic toxicity study.
(inhalation LOAEL = 300 mg/kg/day based on
absorption rate = kidney lesions and death in
100%). males.
UFA = 10x.............
UFH = 10x.............
FQPA SF = 1x..........
---------------------------------------------------------------------------------
Cancer (Oral, dermal, Not expected to be carcinogenic based on the lack of mutagenicity and lack of
inhalation). carcinogenicity in rodents.
----------------------------------------------------------------------------------------------------------------
UFA = extrapolation from animal to human (interspecies). UFH = potential variation in sensitivity among members
of the human population (intraspecies). UFL = use of a LOAEL to extrapolate a NOAEL. UFS = use of a short-term
study for long-term risk assessment. UFDB = to account for the absence of data or other data deficiency. FQPA
SF = Food Quality Protection Act Safety Factor.

C. Exposure Assessment

1. Dietary exposure from food and feed uses. In evaluating dietary
exposure to ethylene glycol, EPA considered exposure under the proposed
exemption from the requirement of a tolerance. EPA assessed dietary
exposures from ethylene glycol in food as follows:
i. Acute and chronic exposure. In conducting the acute and chronic
dietary exposure assessments, EPA used food consumption information
from the United States Department of Agriculture (USDA) 1994-1996 and
1998 Nationwide Continuing Surveys of Food Intake by Individuals
(CSFII). As to residue levels in food, no residue data were submitted
for the ethylene glycol. In the absence of specific residue data, EPA
has developed an approach which uses surrogate information to derive
upper bound exposure estimates for the subject inert ingredient. Upper
bound exposure estimates are based on the highest tolerance for a given
commodity from a list of high-use insecticides, herbicides, and
fungicides. A complete description of the general approach taken to
assess inert ingredient risks in the absence of residue data is
contained in the memorandum entitled ``Alkyl Amines Polyalkoxylates
(Cluster 4): Acute and Chronic Aggregate (Food and Drinking Water)
Dietary Exposure and Risk Assessments for the Inerts.'' (D361707, S.
Piper, 2/25/09) and can be found at http://www.regulations.gov in
docket ID number EPA-HQ-OPP-2008-0738.
In the dietary exposure assessment, the Agency assumed that the
residue level of the inert ingredient would be no higher than the
highest tolerance for a given commodity. Implicit in this assumption is
that there would be similar rates of degradation (if any) between the
active and inert ingredient and that the concentration of inert
ingredient in the scenarios leading to these highest of tolerances
would be no higher than the concentration of the active ingredient.
The Agency believes the assumptions used to estimate dietary
exposures lead to an extremely conservative assessment of dietary risk
due to a series of compounded conservatisms. First, assuming that the
level of residue for an inert ingredient is equal to the level of
residue for the active ingredient will overstate exposure. The
concentration of active ingredient in agricultural products is
generally at least 50 percent of the product and often can be much
higher. Further, pesticide products rarely have a single inert
ingredient; rather there is generally a combination of different inert
ingredients used which additionally reduces the concentration of any
single inert ingredient in the pesticide product in relation to that of
the active ingredient.
Second, the conservatism of this methodology is compounded by EPA's
decision to assume that, for each commodity, the active ingredient
which will serve as a guide to the potential level of inert ingredient
residues is the active ingredient with the highest tolerance level.
This assumption overstates residue values because it would be highly
unlikely, given the high number of inert ingredients, that a single
inert ingredient or class of ingredients would be present at the level
of the active ingredient in the highest tolerance for every commodity.
Finally, a third compounding conservatism is EPA's assumption that all
foods contain the inert ingredient at the highest tolerance level. In
other words, EPA assumed 100 percent of all foods are treated with the
inert ingredient at the rate and manner necessary to produce the
highest residue legally possible for an active ingredient. In summary,
EPA chose a very conservative method for estimating what level of inert
residue could be on food, then used this methodology to choose the
highest possible residue that

[[Page 31476]]

could be found on food and assumed that all food contained this
residue. No consideration was given to potential degradation between
harvest and consumption even though monitoring data shows that
tolerance level residues are typically one to two orders of magnitude
higher than actual residues in food when distributed in commerce.
Accordingly, although sufficient information to quantify actual
residue levels in food is not available, the compounding of these
conservative assumptions will lead to a significant exaggeration of
actual exposures. EPA does not believe that this approach
underestimates exposure in the absence of residue data.
ii. Cancer. Ethylene glycol is not expected to be carcinogenic
since it was negative for carcinogenicity in mice and rats in the
available published studies and there was a negative response for
mutagenicity. Since the Agency has not identified any concerns for
carcinogenicity relating to ethylene glycol, a dietary exposure
assessment to evaluate cancer risk was not performed.
iii. Anticipated residue and percent crop treated (PCT)
information. EPA did not use anticipated residue and/or PCT information
in the dietary assessment for ethylene glycol. Tolerance level residues
and/or 100 PCT were assumed for all food commodities.
2. Dietary exposure from drinking water. For the purpose of the
screening level dietary risk assessment to support this request for an
exemption from the requirement of a tolerance for ethylene glycol, a
conservative drinking water concentration value of 100 parts per
billion (ppb) based on screening level modeling was used to assess the
contribution to drinking water for the chronic dietary risk assessments
for parent compound. These values were directly entered into the
dietary exposure model.
3. From non-dietary exposure. The term ``residential exposure'' is
used in this document to refer to non-occupational, non-dietary
exposure (e.g., textiles (clothing and diapers), carpets, swimming
pools, and hard surface disinfection on walls, floors, tables).
Ethylene glycol may be used in inert ingredients in products that
are registered for specific uses that may result in residential
exposure. A screening level residential exposure and risk assessment
was completed for products containing ethylene glycol as inert
ingredients. The ethylene glycol inerts may be present in consumer
personal (care) products and cosmetics (at concentrations up to 1%)
(http://hpd.nlm.nih.gov/index.htm). The Agency conducted exposure
assessments based on end-use product application methods and labeled
application rates. The Agency conducted an assessment to represent
worst-case residential exposure by assessing ethylene glycol in
pesticide formulations used in crack and crevice applications. The
Agency conducted an assessment to represent worst-case residential
exposure by assessing post application exposures and risks from
ethylene glycol in pesticide formulations.
4. Cumulative effects from substances with a common mechanism of
toxicity. Section 408(b)(2)(D)(v) of FFDCA requires that, when
considering whether to establish, modify, or revoke a tolerance, the
Agency consider ``available information'' concerning the cumulative
effects of a particular pesticide's residues and ``other substances
that have a common mechanism of toxicity.''
EPA has not found ethylene glycol to share a common mechanism of
toxicity with any other substances, and ethylene glycol does not appear
to produce a toxic metabolite produced by other substances. For the
purposes of this tolerance action, therefore, EPA has assumed that
ethylene glycol does not have a common mechanism of toxicity with other
substances. For information regarding EPA's efforts to determine which
chemicals have a common mechanism of toxicity and to evaluate the
cumulative effects of such chemicals, see EPA's Web site at http://www.epa.gov/pesticides/cumulative.

D. Safety Factor for Infants and Children

1. In general. Section 408(b)(2)(C) of FFDCA provides that EPA
shall apply an additional tenfold (10X) margin of safety for infants
and children in the case of threshold effects to account for prenatal
and postnatal toxicity and the completeness of the database on toxicity
and exposure unless EPA determines based on reliable data that a
different margin of safety will be safe for infants and children. This
additional margin of safety is commonly referred to as the FQPA SF. In
applying this provision, EPA either retains the default value of 10X,
or uses a different additional safety factor when reliable data
available to EPA support the choice of a different factor.
2. Prenatal and postnatal sensitivity. In the case of the ethylene
glycol, some of the available studies suggest increased susceptibility
to the offspring of rodents following pre-natal and post-natal
exposure. However, the effects (described in this unit) occurred at
doses that were > 500 mg/kg/day. The established cRfD of 1.5 mg/kg/day
will be protective of these effects. Therefore, the concern for
increased fetal susceptibility is low and there are no residual
concerns.
3. Conclusion. EPA has determined that reliable data show the
safety of infants and children would be adequately protected if the
FQPA SF were reduced to 1X. That decision is based on the following
findings:
i. The toxicity database for ethylene glycol is adequate. The
following acceptable studies are available:
Developmental toxicity studies in rodents (6);
Multi-generation reproduction studies in rodents (4);
Subchronic toxicity studies in multiple species;
Inhalation and dermal toxicity studies;
Chronic/carcinogenicity studies in rodents (5).
ii. Signs of neurotoxicity (when observed) occurred at high doses
and at doses above that which produced kidney toxicity. The established
cRfD of 1.5 mg/kg/day (NOAEL = 150 mg/kg/day) is protective of kidney
toxicity and is therefore protective of neurotoxic effects. Also, the
International Programme on Chemical Safety Concise International
Chemical Assessment Document 45 Ethylene Glycol: Human Health Aspects
(IPCS CICAD 2002) concluded that ``data are limited, results of
identified toxicity studies conducted (via oral, inhalation, or dermal
routes) in rodents, rabbits, and monkeys do not indicate that
neurological effects are critical end-points for ethylene glycol.''
IPCS (2002) also states that generally neurotoxicity effects occur at a
dose higher than the dose producing kidney toxicity. Since the current
cRfD is protective of kidney toxicity, the concern for neurotoxicity is
low to none. Therefore, EPA concluded that the developmental
neurotoxicity is not required.
iii. Evidence of potential immunotoxicity was observed in a
subchronic toxicity study in rats. Decreased relative thymus weights
were observed at 4,000 mg/kg/day. Again, this effect occurred at a high
dose and at a dose above that which produced kidney toxicity. The
established cRfD of 1.5 mg/kg/day (NOAEL = 150 mg/kg/day) is protective
of kidney toxicity and is approximately 2,600 times lower than the dose
where decreased relative thymus weights were observed. Therefore, the
cRfD will be protective of this immunotoxicity effects. The IPCS CICAD
for ethylene glycol finds that although ``data are limited, results of

[[Page 31477]]

identified toxicity studies conducted (via oral, inhalation, or dermal
routes) in rodents, rabbits, and monkeys do not indicate that
immunological effects are critical end-points for ethylene glycol.''
(IPCS 2002).
iv. Evidence of increased susceptibility was not observed in the
developmental toxicity study in the rabbit. However, evidence of
increased susceptibility was observed following prenatal exposure to
ethylene glycol in mice. An increased incidence of total malformations
and bilateral extra rib 14 were observed at 500 mg/kg/day. These
effects occurred in the absence of maternal toxicity. In a
developmental study in rats, there was evidence of qualitative fetal
susceptibility. Maternal (tubular dilation and regeneration in the
kidneys, increased gestational period, and decreased relative kidney
weights) and developmental (decreased pup weight, increased cumulative
mortality/litter, increased incidence of hydrocephaly, decreased
relative kidney weights, decreased absolute brain weights, and
increased incidences of hydrocephaly; defects in ribs, sternebrae, and
vertebrae) were observed at the same dose (1,250 mg/kg/day). There was
no evidence of increased fetal susceptibility in another developmental
study in rats, maternal (pre-implantation loss) and developmental
(poorly ossified and unossified vertebral centra) effects were observed
at the same dose (1,000 mg/kg/day). However, there was a well
established NOAEL in these two developmental toxicity studies in rats
protecting fetuses. In addition, these fetal effects were generally
seen at relatively high doses. In a reproduction study in mice,
increased fetal susceptibility was observed but again it occurred above
the limit dose. Developmental toxicity manifested as decrease number of
live pups/litter, and mean live pup weight was observed in the absence
of maternal toxicity at 1,640 mg/kg/day.
In another reproduction study in mice, maternal (kidney lesions and
oxalate crystals) and developmental toxicity (decrease in pup weight
adjusted for litter size) were observed at 897 mg/kg/day.
However, the concern for this increased susceptibility was low
based on the following rationale:
a. There is a well established NOAEL in these studies protecting
fetuses/offspring from the aforementioned effects;
b. Although increased susceptibility was observed, this occurred at
doses close to the limit dose of 1,000 mg/kg/day;
c. The effects seen in the developmental study were not reproduced
in the reproduction studies; and
d. The established chronic reference dose of 1.5 mg/kg/day will be
protective of these effects. Therefore, based on the weight of evidence
the concern for increased fetal susceptibility is low.
v. There are no residual uncertainties identified in the exposure
databases. The dietary food exposure assessments were performed using
very conservative assumptions. EPA made conservative (protective)
assumptions in the ground water and surface water modeling used to
assess exposure to ethylene glycol in drinking water. EPA used
similarly conservative assumptions to assess post-application exposure
of children as well as incidental oral exposure of toddlers. These
assessments will not underestimate the exposure and risks posed by
ethylene glycol.

E. Aggregate Risks and Determination of Safety

EPA determines whether acute and chronic dietary pesticide
exposures are safe by comparing aggregate exposure estimates to the
aPAD and cPAD. For linear cancer risks, EPA calculates the lifetime
probability of acquiring cancer given the estimated aggregate exposure.
Short-, intermediate-, and chronic-term risks are evaluated by
comparing the estimated aggregate food, water, and residential exposure
to the appropriate PODs to ensure that an adequate MOE exists.
1. Acute risk. An acute aggregate risk assessment takes into
account acute exposure estimates from dietary consumption of food and
drinking water. Using the exposure assumptions described in this unit
for acute exposure, EPA has concluded that acute exposure to ethylene
glycol from food and water will utilize 26.5% of the aPAD for females
13-49, the only population group identified as potentially facing an
acute risk from exposure to ethylene glycol.
2. Chronic risk. Using the exposure assumptions described in this
unit for chronic exposure, EPA has concluded that chronic exposure to
ethylene glycol from food and water will utilize 12.8% of the cPAD for
the general population and 41.6% of the cPAD for children 1-2 yrs old,
the population group receiving the greatest exposure.
3. Short-term risk. Short-term aggregate exposure takes into
account short-term residential exposure plus chronic exposure to food
and water (considered to be a background exposure level).
Ethylene glycol is currently used as an inert ingredient in
pesticide products that are registered for uses that could result in
short-term residential exposure, and the Agency has determined that it
is appropriate to aggregate chronic exposure through food and water
with short-term residential exposures to ethylene glycol.
Using the exposure assumptions described in this unit for short-
term exposures, EPA has concluded the combined short-term food, water,
and residential exposures result in aggregate MOEs of 200 for both
adult males and females, respectively. Adult residential exposure
combines high end dermal and inhalation handler exposure from homeowner
mixer/loader/applicators using a trigger sprayer with a high end post
application dermal exposure from contact with treated lawns. EPA has
concluded that the combined short-term aggregated food, water, and
residential exposures result in an aggregate MOE of 170 for children.
Children's residential exposure includes total exposures associated
with contact with treated surfaces (dermal and hand-to-mouth
exposures). Because EPA's LOC for ethylene glycol is a MOE of 100 or
below, these MOEs are not of concern.
4. Intermediate-term risk. Intermediate-term aggregate exposure
takes into account intermediate-term residential exposure plus chronic
exposure to food and water (considered to be a background exposure
level).
Ethylene glycol is currently used as an inert ingredient in
pesticide products that are registered for uses that could result in
intermediate-term residential exposure, and the Agency has determined
that it is appropriate to aggregate chronic exposure through food and
water with intermediate-term residential exposures to ethylene glycol.
Using the exposure assumptions described in this unit for
intermediate-term exposures, EPA has concluded that the combined
intermediate-term food, water, and residential exposures result in
aggregate MOEs of 580 for both adult males and females, respectively.
Adult residential exposure combines high end dermal and inhalation
handler exposure from homeowner mixer/loader/applicators using a
trigger sprayer with a high end post application dermal exposure from
contact with treated lawns. EPA has concluded that the combined short-
term aggregated food, water, and residential exposures result in an
aggregate MOE of 200 for children. Children's residential exposure
includes total exposures associated with contact with treated surfaces
(dermal and hand-to-mouth exposures). Because EPA's LOC for ethylene
glycol is a MOE of 100

[[Page 31478]]

or below, these MOEs are not of concern.
5. Aggregate cancer risk for U.S. population. The Agency has not
identified any concerns for carcinogenicity relating to ethylene
glycol.
6. Determination of safety. Based on these risk assessments, EPA
concludes that there is a reasonable certainty that no harm will result
to the general population, or to infants and children, from aggregate
exposure to ethylene glycol residues.

V. Other Considerations

A. Analytical Enforcement Methodology

An analytical method is not required for enforcement purposes since
the Agency is establishing an exemption from the requirement of a
tolerance without any numerical limitation.

B. International Residue Limits

In making its tolerance decisions, EPA seeks to harmonize U.S.
tolerances with international standards whenever possible, consistent
with U.S. food safety standards and agricultural practices. EPA
considers the international maximum residue limits (MRLs) established
by the Codex Alimentarius Commission (Codex), as required by FFDCA
section 408(b)(4). The Codex Alimentarius is a joint U.N. Food and
Agriculture Organization/World Health Organization food standards
program, and it is recognized as an international food safety
standards-setting organization in trade agreements to which the United
States is a party. EPA may establish a tolerance that is different from
a Codex MRL; however, FFDCA section 408(b)(4) requires that EPA explain
the reasons for departing from the Codex level.
The Codex has not established a MRL for ethylene glycol.

C. Response to Comments

The two comments were received from private citizens who opposed
the authorization to sell any pesticide that leaves a residue on food.
The Agency understands the commentors' concerns and recognizes that
some individuals believe that no residue of pesticides should be
allowed. However, under the existing legal framework provided by
section 408 of FFDCA, EPA is authorized to establish pesticide
tolerances or exemptions where persons seeking such tolerances or
exemptions have demonstrated that the pesticide meets the safety
standard imposed by the statute.

VI. Conclusions

Therefore, an exemption from the requirement of a tolerance is
established under 40 CFR 180.910 for ethylene glycol (107-21-1) when
used as an inert ingredient (in encapsulating agents for pesticides
being applied post-harvest as residual, and crack and crevice sprays in
and around food and nonfood areas of residential and nonresidential
structures, including food handling establishments) and 40 CFR 180.920
for ethylene glycol when used as an (inert ingredient as a solvent,
stabilizer and/or antifreeze within pesticide formulations/products
without limitation) applied to pre-harvest crops.

VII. Statutory and Executive Order Reviews

This final rule establishes a tolerance under section 408(d) of
FFDCA in response to a petition submitted to the Agency. The Office of
Management and Budget (OMB) has exempted these types of actions from
review under Executive Order 12866, entitled Regulatory Planning and
Review (58 FR 51735, October 4, 1993). Because this final rule has been
exempted from review under Executive Order 12866, this final rule is
not subject to Executive Order 13211, entitled Actions Concerning
Regulations That Significantly Affect Energy Supply, Distribution, or
Use (66 FR 28355, May 22, 2001) or Executive Order 13045, entitled
Protection of Children from Environmental Health Risks and Safety Risks
(62 FR 19885, April 23, 1997). This final rule does not contain any
information collections subject to OMB approval under the Paperwork
Reduction Act (PRA), 44 U.S.C. 3501 et seq., nor does it require any
special considerations under Executive Order 12898, entitled Federal
Actions to Address Environmental Justice in Minority Populations and
Low-Income Populations (59 FR 7629, February 16, 1994).
Since tolerances and exemptions that are established on the basis
of a petition under section 408(d) of FFDCA, such as the tolerance in
this final rule, do not require the issuance of a proposed rule, the
requirements of the Regulatory Flexibility Act (RFA) (5 U.S.C. 601 et
seq.) do not apply.
This final rule directly regulates growers, food processors, food
handlers, and food retailers, not States or tribes, nor does this
action alter the relationships or distribution of power and
responsibilities established by Congress in the preemption provisions
of section 408(n)(4) of FFDCA. As such, the Agency has determined that
this action will not have a substantial direct effect on States or
tribal governments, on the relationship between the national government
and the States or tribal governments, or on the distribution of power
and responsibilities among the various levels of government or between
the Federal Government and Indian tribes. Thus, the Agency has
determined that Executive Order 13132, entitled Federalism (64 FR
43255, August 10, 1999) and Executive Order 13175, entitled
Consultation and Coordination with Indian Tribal Governments (65 FR
67249, November 9, 2000) do not apply to this final rule. In addition,
this final rule does not impose any enforceable duty or contain any
unfunded mandate as described under Title II of the Unfunded Mandates
Reform Act of 1995 (UMRA) (Pub. L. 104-4).
This action does not involve any technical standards that would
require Agency consideration of voluntary consensus standards pursuant
to section 12(d) of the National Technology Transfer and Advancement
Act of 1995 (NTTAA), Public Law 104-113, section 12(d) (15 U.S.C. 272
note).

VIII. Congressional Review Act

The Congressional Review Act, 5 U.S.C. 801 et seq., generally
provides that before a rule may take effect, the agency promulgating
the rule must submit a rule report to each House of the Congress and to
the Comptroller General of the United States. EPA will submit a report
containing this rule and other required information to the U.S. Senate,
the U.S. House of Representatives, and the Comptroller General of the
United States prior to publication of this final rule in the Federal
Register. This final rule is not a ``major rule'' as defined by 5
U.S.C. 804(2).

List of Subjects in 40 CFR Part 180

Environmental protection, Administrative practice and procedure,
Agricultural commodities, Pesticides and pests, Reporting and
recordkeeping requirements.

Dated: May 18, 2011.
Lois Rossi,
Director, Registration Division, Office of Pesticide Programs.

Therefore, 40 CFR chapter I is amended as follows:

PART 180--[AMENDED]

0
1. The authority citation for part 180 continues to read as follows:

Authority: 21 U.S.C. 321(q), 346a and 371.

0
2. In Sec. 180.910, the table is amended by adding alphabetically the
following inert ingredient to read as follows:

[[Page 31479]]

Sec. 180.910 Inert ingredients used pre- and post-harvest; exemptions
from the requirement of a tolerance.

* * * * *

----------------------------------------------------------------------------------------------------------------
Inert ingredients Limits Uses
----------------------------------------------------------------------------------------------------------------

* * * * * * *
Ethylene glycol (CAS Reg. No. 107-21- Without limitation..... Encapsulating agent for pesticides being
1). applied post-harvest as residual, and crack
and crevice sprays in and around food and
nonfood areas of residential and
nonresidential structures, including food
handling establishments.

* * * * * * *
----------------------------------------------------------------------------------------------------------------

0
3. In Sec. 180.920, the table is amended by adding alphabetically the
following inert ingredient to read as follows:

Sec. 180.920 Inert ingredients used pre-harvest; exemptions from the
requirement of a tolerance.

* * * * *

* * * * * * *
Ethylene glycol (CAS Reg. No. 107-21-1) Without limitation..... Pesticide inert ingredient as a solvent,
stabilizer and/or antifreeze.

* * * * * * *
----------------------------------------------------------------------------------------------------------------

[FR Doc. 2011-13577 Filed 5-31-11; 8:45 am]
BILLING CODE 6560-50-P